Broad spectrum macrocyclic lactones, for example, avermectins and milbemycin, are antiparasitic agents with anthelmintic, endoparasiticide, ectoparasiticide, acaricide, and insecticide utility. Parasites which may be controlled with these broad spectrum agents include: gastrointestinal roundworms (e.g., Ostertagia spp., Haemonchus spp., Trichostrongylus spp., Cooperia spp., Bunostomum spp., Strongyloides spp., Oesophagostomum spp., and Trichuris spp.); lungworms (e.g., Dictyocaulus viviparus); eyeworms (e.g., Thelazia spp.); parasitic stage grubs (e.g., Hypoderma spp.), and Dermatobia hominis); biting and sucking lice (e.g., Damalinia bovis, Haematopinus eurystemus, Linognathus vituli and Solenopotes capillatus); ticks (e.g., Rhipicephalus (Boophilus) microplus); mites (e.g., Psoroptes bovis and Sarcoptes scabiei); screwworm (e.g., Cochliomyia hominivorax); and horn flies (e.g., Haematobia irritans).
U.S. Pat. Nos. 6,063,394, 6,699,847, and U.S. Pat. No. 6,617,314 relate to injectable compositions containing avermectins and/or milbemycin in triglyceride oils (sesame, castor, fractionated coconut oil), ethyl oleate; medium-chain triglycerides or glycol esters or fatty acid esters; co-solvents selected from mono- or polyhydric aliphatic or aromatic alcohols and their derivatives; and auxiliaries such as antioxidants and preservatives.
U.S. Pat. No. 6,174,540 relates to a long acting injectable composition comprising a therapeutic agent selected from the group consisting of insecticides, acaricides, parasiticides, growth enhancers, and oil soluble NSAIDS; hydrogenated castor oil; and a hydrophobic carrier comprising triacetin, benzyl benzoate, or ethyl oleate, or combinations thereof; and acylated monoglycerides, various medium chain esters, or a combination thereof.
U.S. Pat. No. 5,089,480 relates to avermectins and compositions thereof. U.S. Pat. No. 6,001,822 relates to a pharmaceutical composition comprising a solution of doramectin in a solvent consisting of sesame oil and ethyl oleate. An injectable doramectin composition containing 1% (w/v) doramectin (10 mg/mL) in a combination of sesame oil and ethyl oleate is sold by Pfizer under the trade name Dectomax® for the treatment of parasitic infections in cattle.
Following treatment, residual macrocyclic lactones can be found in animal tissue for extended periods of time. Thus, when an animal is treated with a macrocyclic lactone there is a withhold time in which the animal cannot be slaughtered for human consumption. Specifically, when beef cattle are given a single dose of doramectin at the recommended dose of 200 μg/Kg of body weight, which is equivalent to 10 mg/110 pounds of body weight, the withhold time is 35 days.
Further, it is known that numerous parasites can and have become resistant to many of the current commercial antiparasitic products. In an effort to combat resistance, higher doses of the antiparasitic agents have been formulated. As described above, averemectins and milbemycin have been formulated with castor oil and ethyl oleate because of their increased solubility. Subsequently, high solubility equates to a high oil affinity which affects the release rate of the drug from the oil. As drug concentration increases, there is a slower release rate which is associated with a longer withhold time. In some instances, high doses of avermectin and milbemycin will precipitate out of solution as a result of a low partition coefficient between oil and drug. If this occurs, residual drug concentrations at the injection site can be high. Thus, absorption and release rate is slow and withhold time is extended. Therefore, cattle dosed with higher concentrations of avermectins and/or milbemycin can not be timely slaughtered thereby increasing herd management costs and subsequently consumer cost. The compositions of the present invention provide a high dose of an avermectin and/or milbemycin, preferably doramectin, that provides increased efficacy against parasites with a substantially shorter withhold time.
All of the above recited U.S. patents and publications are incorporated herein by reference.